rs1312663828

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The ENST00000253122.10(SLC6A8):​c.1597-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000662 in 1,209,181 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 24)
Exomes 𝑓: 0.0000064 ( 0 hom. 1 hem. )

Consequence

SLC6A8
ENST00000253122.10 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.00002352
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -6.97
Variant links:
Genes affected
SLC6A8 (HGNC:11055): (solute carrier family 6 member 8) The protein encoded by this gene is a plasma membrane protein whose function is to transport creatine into and out of cells. Defects in this gene can result in X-linked creatine deficiency syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.96).
BP6
Variant X-153694715-G-A is Benign according to our data. Variant chrX-153694715-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 533704.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC6A8NM_005629.4 linkuse as main transcriptc.1597-4G>A splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000253122.10 NP_005620.1
SLC6A8NM_001142805.2 linkuse as main transcriptc.1567-4G>A splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant NP_001136277.1
SLC6A8NM_001142806.1 linkuse as main transcriptc.1252-4G>A splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant NP_001136278.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC6A8ENST00000253122.10 linkuse as main transcriptc.1597-4G>A splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_005629.4 ENSP00000253122 P1P48029-1
SLC6A8ENST00000430077.6 linkuse as main transcriptc.1252-4G>A splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 2 ENSP00000403041 P48029-4
SLC6A8ENST00000485324.1 linkuse as main transcriptn.1904-4G>A splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.00000889
AC:
1
AN:
112511
Hom.:
0
Cov.:
24
AF XY:
0.0000288
AC XY:
1
AN XY:
34691
show subpopulations
Gnomad AFR
AF:
0.0000323
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000638
AC:
7
AN:
1096670
Hom.:
0
Cov.:
38
AF XY:
0.00000276
AC XY:
1
AN XY:
362716
show subpopulations
Gnomad4 AFR exome
AF:
0.0000379
Gnomad4 AMR exome
AF:
0.0000284
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000594
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000889
AC:
1
AN:
112511
Hom.:
0
Cov.:
24
AF XY:
0.0000288
AC XY:
1
AN XY:
34691
show subpopulations
Gnomad4 AFR
AF:
0.0000323
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000529

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Creatine transporter deficiency Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpSep 12, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.96
CADD
Benign
0.0050
DANN
Benign
0.33

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000024
dbscSNV1_RF
Benign
0.018
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1312663828; hg19: chrX-152960170; API